Glioblastoma (GBM), the most common primary malignant brain tumor, is associated with a dismal prognosis. Standard therapies including maximal surgical resection, radiotherapy, and temozolomide chemotherapy remain poorly efficient. Improving GBM treatment modalities is, therefore, a paramount challenge for researchers and clinicians. GBMs exhibit the hallmark feature of aggressive invasion into the surrounding tissue. Among cell surface receptors involved in this process, members of the integrin family are known to be key actors of GBM invasion. Upregulation of integrins was reported in both tumor and stromal cells, making them a suitable target for innovative therapies targeting integrins in GBM patients, as their impairment disrupts tumor cell proliferation and invasive capacities. Among them, integrin-αvβ3 expression correlates with high-grade GBM. Driven by a plethora of preclinical biological studies, antagonists of αvβ3 rapidly became attractive therapeutic candidates to impair GBM tumorigenesis. In this perspective, the advent of nuclear medicine is currently one of the greatest components of the theranostic concept in both preclinical and clinical research fields. In this review, we provided an overview of αvβ3 expression in GBM to emphasize the therapeutic agents developed. Advanced current and future developments in the theranostic field targeting αvβ3 are finally discussed.

Medulloblastoma (MB) is the most frequent solid tumor in children, localized in the brain posterior fossa. Its standard of care comprises maximal resection surgery followed by craniospinal irradiation and chemotherapy. Despite a long-term survival rate of 70%, wide disparities among patients have been observed. Relevant targets for naive and recurrent MB are urgently needed. Primary and recurrent MBs are characterized by aggressive invasion into surrounding brain tissue, active angiogenesis, and radioresistance. Integrin-alpha v beta 3 was a major driver of these features in glioblastoma. Nevertheless, such observations have not yet been reported in MB. Integrin alpha v beta 3 was found to be expressed in a subset of MB patients. We investigated the role of integrin-alpha v beta 3 using MB-derived cell lines with beta 3 -subunit depletion or overexpression both in vitro and in vivo. Radioresistant MB cell lines were generated and showed increased integrin-alpha v beta 3 expression, which correlated with increased susceptibility to pharmacological integrin-alpha v beta 3 inhibition with cilengitide, a competitive ligand mimetic. Finally, we conducted single-photon emission computed tomography (SPECT)/magnetic resonance imaging (MRI) studies on orthotopic models using a radiolabeled integrin-alpha v beta 3 ligand (99mTc-RAFT-RGD). This approach offers the prospect of a novel predictive imaging modality in MB. Altogether, our data pave the way for SPECT/MRI-based selection of a subpopulation of MB patients eligible for integrin-alpha v beta 3-directed therapies.